Aetiology of spinal deformities in neurofibromatosis 1: new hypotheses

Neurofibromatosis 1 is a common heritable disorder. The gene causing neurofibromatosis 1 had been recognized and the protein encoded by this gene, neurofibromin, was supposed to play a role in development of various tissues. Neurofibromin was found to have GTP-ase (GAP) domain against small p21 ras. IQGAP1 is another human ras-specific GAP that was found to have calmodulin-binding motifs. Spinal deformities in cases of neurofibromatosis 1 are generally classified into dystrophic and non-dystrophic. Aetiologies of both types are still unknown. We hypothesize that muscle pathology could be the initiating factor for non-dystrophic curves due to neurofibromin deficiency and/or increase of the level of IQGAP. Dystrophic curves might begin as a developmental error due to neurofibromin deficiency in bone. Melatonin deficiency, increased serotonin level with disturbed melatonin-serotonin interactions and calmodulin antagonism by increased IQGAP1 may be responsible for progression of both types of spinal deformities in neurofibromatosis 1.